Efficient Multigram Synthesis of the Repeating Unit of Gallic Acid-Triethylene Glycol Dendrimers

Abstract

A multigram synthesis of the repeating unit of GATG (gallic acid-triethylene glycol) dendrimers is described through an efficient and cost-effective route. These conditions overcome major problems precluding scaling up and afford product in excellent overall yield and purity. Special attention has been paid in this process to green chemistry principles: atom economy, safety, and waste reduction. This scheme could be easily adapted for the preparation of similar dendritic systems.

The Effect of PEGylation on Multivalent Binding: A Surface Plasmon Resonance and Isothermal Titration Calorimetry Study with Structurally Diverse PEG‐Dendritic GATG Copolymers

“…PEG 20 000 ‐4OH ( M n 20 594, M w 20 616 by MALDI‐TOF) was obtained from Nektar. 3,4,5‐Tri‐[2‐[2‐(2‐azidoethoxy)ethoxy]ethoxy]benzoic acid (GATG repeating unit), tert ‐butyl (2‐(2‐(2‐aminoethoxy)ethoxy)ethyl)carbamate and 2‐propynyl α‐ l ‐fucopyranoside (Fuc‐Alk) were prepared following previously reported procedures. UEA‐I was purchased from Vector laboratories.…”

Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA

“…(azidetriethylene glycol), 3,4,5-Tri-(2-(2-(2azidoethoxy)ethoxy)ethyl)benzoic acid (GATG building unit 7), and generations 1 and 2 of hydrolytically stable PEG-GATG dendritic block copolymers were prepared following protocols previously reported by us. 47,48 K2CO3 was dried under reduced pressure at 65 °C.…”

“…Despite the presence of degradable/hydrolyzable ester bonds hinders its synthesis, building unit 5 was efficiently synthesized from commercially available chlorotriethylene glycol (3), 4-bromobutanoic acid and gallic acid (1). Initial treatment of 4-bromobutanoic acid with azidetriethylene glycol (easily obtained from 3 and NaN3) 47 with DCC and DMAP led to ester 4 in an excellent 97 % combined yield. Subsequent coupling of 4 with tert-butyl gallate (2) (K2CO3, 18C6) followed by a selective hydrolysis of the tert-butyl ester afforded the desired biodegradable building unit 5 in 82 % overall yield (Figure 2a).…”

GATG Dendrimers and PEGylated Block Copolymers: from Synthesis to Bioapplications

“…By observing green chemistry principles (atom economy, safety, waste reduction), this synthetic route has been further developed for the cost-effective production of the repeating unit in batches larger than 100 g in excellent overall yield (86%) and purity ( Fig. 1) (1). With an easy and scalable access to the repeating unit, the preparation of GATG dendrimers and PEG-dendritic block copolymers has been efficiently achieved in large quantities up to G4 (243 peripheral azides) (33)(34)(35).…”

“…Structure, synthesis of the repeating unit, and applications of GATG dendrimers. Reprinted with permission from reference (1) wedges to render PEG-GATG block copolymers with increased solubility and stealth properties. PEG-dendritic block copolymers constitute interesting hybrid structures where differences in the solubility properties of the blocks can be exploited in the preparation of micelles and other nanostructures of biomedical interest (30)(31)(32).…”